This is a continuation of a study of the roles played by certain enzymes of pyruvate metabolism in genetic disease. The principal enzymes involved are pyruvate carboxylase, pyruvate dehydrogenase complex and PEP carboxykinase. The aim is to develop methods for the accurate detection of inborn errors involving these enzymes and also to develop methods for correlating such defects with the physiological effects on the individuals with the disease. Present studies are concentrating mainly on the measurement of pyruvate dehydrogenase complex and its various components, mainly in cultured fibroblasts. Such methods will be applied to known and suspected cases of pyruvate dehydrogenase deficiency.